Senile cataract is the third leading cause of legal blindness in the United States. The prevention or slowing of cataract development or the discovery of non-surgical treatment is a desirable goal. The National Eye Institute has estimated that a 10-year delay in the need for a cataract operation would save $608 million annually (1 982). The etiology of age-related or senile cataract is not known. However, oxidations of cellular components, lipid and protein, of the lens plasma membrane by peroxides and free radicals occur in this process and subsequent disruption of transmembrane ion gradients leads to abnormal cell function. Exaggeration or acceleration of age-related oxidative injury may in part cause 70% of all cataracts. Access to a controlled delivery of oxidative stress to the lens in an animal model enables opportunity to better define the relationship of oxidation to cataractogenesis and to discover and to assess effectiveness of preventive regimens. Systemic delivery of sodium selenite to the lens generates a mature nuclear opacity within 3-4 days as well as postsubcapsular and cortical opacities which appear at other times. A 3-5 fold increase in lens calcium causes the nuclear cataract. Preweaning rats are used in this very reliable and reproducible model, since, beyond the age of 21 days, either the delivery of selenite to the lens or the uptake of -selenite by the lens is diminished 5-fold. We present evidence that reduction of selenite by glutathione generates superoxide anion and other free radicals and leads to oxidative injury of components of systems responsible for ion homeostasis. We propose a systematic study of the effect of selenite on these specific processes which regulate Ca and Na homeostasis in the rat lens. Further we propose to identify and characterize the oxidant species and test the ability of various antioxidants to provide systemic protection against selenite cataract.